The overall objectives are to study the local control of bone resorption, specifically the relationships between mononuclear cells (lymphocytes and monocytes) and the origin, structure and function of osteoclasts and the role of mononuclear cells and borne resorption in tooth eruption. The specific aims are to use the demonstrated dependence of osteoclast function in ia (osteopetrotic) rats on mononuclear cells from normal littermtes as a probe to explore the origin, structure and function of osteoclasts, certain relationships between macrophages and osteoclasts and the contribution of mononuclear cells and bone resorption to tooth eruption. The possibility that mononuclear cells contribute to bone resorption directly by differentiation into osteoclasts is to be studied by using autoradiography to follow the fate of 3H-thymidine labelled mononuclear cells from normal rats in ia littermate hosts during restoration of bone resorption. The possibility that mononuclear cells restore function of osteoclasts in ia rats by elaborating a local factor (s) will be pursued by implanting mononuclear cells from normal rats in Millipore chambers next to a bone surface in ia rats and studying the effects of host osteoclasts in the vicinity. The mononuclear cell pool responsible for the cure will be dissected by cell separation techniques and the ability of T-cell and monocyte-enriched preparations are to be tested for their ability to restore bone resorption in newborn ia rats, a time when cure of the disease is possible without irradiation of the host. Macrophage/osteoclast relationships will be pursued in the ia rat by studying macrophage structure, function and differentiation to determine if this mutation affects macrophages in addition to osteoclasts. Finally, the presumed dependence of tooth eruption on bone resorption will be tested in the ia rat, in which incisors and first molars do not erupt and bone resorption is reduced by curing the disease at birth and observing the effect on tooth eruption.